MTHFR 677TT is associated with decreased number of embryos and cumulative live birth rate in patients undergoing GnRHa short protocol: a retrospective study
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Abstract Background Whether MTHFR C677T genotype affects pregnancy outcomes following assisted reproductive technology is conflicting. And the role of MTHFR C677T genotype on cumulative live birth has not been reported. This study aims to investigate the effect of MTHFR C677T genotype on cumulative live birth following in-vitro fertilization and embryo transfer (IVF-ET). Methods This is a retrospective cohort study that includes 1173 women undergoing their first IVF-ET. We retrospectively compared the reproductive outcomes among the groups stratified by MTHFR C677T genotypes (677CC, 677CT, 677TT). We performed interaction analysis to detect the factor that interacts with the MTHFR C677T genotype. Poisson regression analyses were used to evaluate the associations between MTHFR C677T genotypes with the number of transferable embryos and the number of good-quality embryos. Cox regression analysis was used to evaluate the association between MTHFR C677T genotypes with cumulative live birth. All regression analyses were adjusted with the confounding factors which may independently impact reproductive outcomes. Results There is a significant interactive effect of MTHFR 677TT genotype with GnRHa protocol on reproductive outcomes (P for interaction<0.05). MTHFR 677TT homozygous mutation was found to impact reproductive outcomes under GnRHa short protocol but not GnRHa long protocol. MTHFR 677TT is significantly associated with decreased number of transferable embryos ( p -value=0.028), decreased number of good-quality embryos ( p -value=0.005), and decreased cumulative live birth rate ( p -value=0.024) in patients undergoing GnRHa short protocol. However, the clinical pregnancy rate, miscarriage rate and live birth rate at the first embryo transfer cycle were not significantly different between the groups under both protocols ( p -values>0.05). Conclusions MTHFR 677TT genotype is associated with decreased number of transferable embryos, decreased number of good-quality embryos, and decreased cumulative live birth rate in the first complete cycle in patients undergoing GnRHa short protocol.Keywords:
Live birth
최근에 신부전 환자들의 심혈관 질환의 발생은 혈중 호모시스테인 농도와 관련이 없고 5,10-Methylenetetrahydrofolate reductase (MTHFR) C677T 유전자 다형성과 관련이 있다는 보고가 나오고 있다. MTHFR 유전자 다형성이 혈중 호모시스테인의 농도를 증가시킨다는 기존의 의미 외에, 그 자체로 죽상동맥경화증이나 심혈...
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Methylene tetrahydrofolate reductase (MTHFR) is a key enzyme of homocysteine metabolism participating in the folate cycle. The aim of this study was to investigate the association of MTHFR C677T and MTHFR A1298C gene polymorphisms with serum folate, cobalamin (Cbl) and homocysteine (Hcy) concentrations in healthy Greek adults. The MTHFR C677T and A1298C gene polymorphisms were genotyped in 383 healthy Greek adults (199 men and 184 women) using polymerase chain reaction and reverse hybridization. Serum folate, Cbl and total Hcy (tHcy) levels were determined using immunoassays methods. Among the 383 individuals, 73 (19.1%) were normal (CC), 202 (52.7%) were heterozygous (CT) and 108 (28.2%) were homozygous (TT) regarding the MTHFR C677T gene polymorphism, while 263 (68.7%) were normal (AA), 105 (27.4%) were heterozygous (AC) and 15 (3.9%) were homozygous (CC) regarding the MTHFR A1298C gene polymorphism. The overall C and T allele frequency for the MTHFR C677T gene polymorphism was 45.4% and 54.6%, respectively, while the overall A and C allele frequency for the MTHFR A1298C gene polymorphism was 82.3% and 17.6%, respectively. The MTHFR C677T and not the A1298C gene polymorphism had a significantly influence on serum folate and tHcy levels. The individuals with 677TT genotype had significantly lower serum folate and significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. Serum folate and tHcy levels are influenced by the existence of the MTHFR C677T gene polymorphism (mainly 677TT genotype). Individuals with low serum folate levels and/or high serum tHcy levels should be further investigated for a possible existence of MTHFR C677T and not A1298C gene polymorphisms, with aim to determine the suitable treatment.
Gene polymorphism
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Oocyte cryopreservation
Live birth
Assisted Reproductive Technology
Embryo cryopreservation
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Genetic predisposition
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Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C mutations, being considered unfavourable genetic factors by causing elevated serum homocysteine levels, may be risk factors for cardiovascular disorders, including ischaemic stroke. In this study, the role of these two mutations in ischaemic stroke was examined:Genetic and clinical data were analysed of 122 ischaemic stroke patients and 102 control subjects with no lesions by neuroimaging.Neither of the two MTHFR mutations alone was found to be a significant genetic risk factor for ischaemic stroke. However, at least one MTHFR 677T allele combined with at least one MTHFR 1298C allele significantly increased the risk of ischaemic stroke (adjusted odds ratio: 3.39; p < 0.001).The synergistic effect between the two MTHFR mutations may represent a new genetic stoke risk factor.
Ischaemic stroke
Stroke
Hyperhomocysteinemia
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The one-carbon metabolism pathway disorder was important role in successful pregnancy. The MTHFR and TS protein were crucial factor in one-carbon metabolism. To investigate the association between recurrent implantation failure (RIF) and enzymes in the one-carbon metabolism pathway. A total of 120 women diagnosed with RIF and 125 control subjects were genotyped for MTHFR 677C>T, 1298A>C, TSER 2R/3R and TS 1494del/ins by a polymerase chain reaction-restriction fragment length polymorphism assay. According to the gene-gene combination analysis, the MTHFR 677/MTHFR 1298 (TT/AA) and MTHFR 677/TS 1494 (TT/6bp6bp) genetic combinations were associated with relatively higher risks [adjusted odds ratio (AOR), 2.764; 95% CI, 1.065-7.174; P = 0.037 and AOR, 3.186; 95% CI, 1.241-8.178; P = 0.016] in RIF patients compared to the CC/AA (MTHFR 677/MTHFR 1298) and TT/6bp6bp (MTHFR 677/TS 1494) combinations, respectively. The results suggested that the combined MTHFR 677/MTHFR 1298 genotype might be associated with increased risk of RIF. To the best of our knowledge, this study is the first to elucidate the potential association of MTHFR, TS and TSER polymorphisms with RIF risk in Korean patients.
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Background The methylenetetrahydrofolate reductase ( MTHFR ) polymorphism is a risk factor for neural tube defects. C677T and A1298C MTHFR polymorphisms produce an enzyme with reduced folate‐related one carbon metabolism, and this has been associated with aberrant methylation modifications in DNA and protein. Methods A meta‐analysis was conducted to assess the association between MTHFR C677T/A1298C genotypes and global genomic methylation. Results Eleven studies met the inclusion criteria. Of these, 10 were performed on C677T MTHFR genotypes and 6 were performed on A1298C MTHFR genotypes. Our results did not indicate any correlation between global methylation and MTHFR A1298C, C677T polymorphisms. Conclusion The results of our study provide evidence to assess the global methylation modification alterations of MTHFR polymorphisms among individuals. However, our data did not found any conceivable proof supporting the hypothesis that common variant of MTHFR A1298C, C677T contributes to methylation modification. Birth Defects Research (Part A) 106:667–674, 2016. © 2016 Wiley Periodicals, Inc.
genomic DNA
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Methylenetetrahydrofolate reductase (MTHFR ) is an enzyme that plays a key role in regulation of folate and homocysteine metabolism. The body utilizes MTHFR to catalyze the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is the primary circulatory form of folate and is utilized in the homocysteine remethylation to methionine. This chapter reviews the physiology related to MTHFR ; discusses the interpretation; reviews the available evidence; and provides clinical pearls from practicing clinicians. Laboratory testing for MTHFR evaluates the presence or absence of the C677T and/or A1298C mutations by means of DNA analysis. Other possible mutations may be possible but are rarely encountered. MTHFR evaluation is usually ordered in response to elevated homocysteine levels, especially in combination with cardiovascular disease, inappropriate thrombosis, or recurrent pregnancy loss. However, MTHFR testing is not recommended for patients with blood clots due to its limited utility.
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Folate metabolism is thought to play an important role in lung cancer through its involvement in both DNA methylation and nucleotide synthesis.Methylenetetrahydrofolate reductase(MTHFR) is an important folate metabolizing enzyme that catalyzes methylenetetrahydrofolate into 5-methyltetrahydrofolate,which is the methyl donor for remethylation of homocysteine to methionine.Certain common polymorphisms within the MTHFR gene(C677T,A1298C) result in reduced enzymatic activity and have been associated with reduced risk for a variety of disease.According to former experiments,MTHFR polymorphisms are associated with lung cancer which is also affected with lots of other elements.This article summarized several conclusions of different experiments involving MTHFR polymorphisms and lung cancer.
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